SPECIFIC AIMS The overall goal of this project is to develop a better understanding and improved quantitative characterization of the complex dynamics that result from abnormal regulation of the respiratory, cardiovascular and metabolic control systems in important chronic diseases or clinical syndromes, such as hypertension. Type 2 diabetes, sickle cell disease, metabolic syndrome, and sleep disordered breathing (SDB). These problems will be addressed by employing a combination of structured (parametric) modeling and minimal (non-parametric) modeling approaches that we have successfully applied in previous cycles of this grant. The proposed project will build on the work that has been accomplished in the current funding cycle, addressing several important issues that remain unresolved and extending our modeiing efforts to more clinical applications. There are three major emphases in our proposed studies. The first pertains to developing models that can characterize the dynamics of the interactions among the participating physiological control systems (eg. respiratory, cardiovascular, metabolic and renal) as they are altered with time because of disease progression or therapy. The second lends recognition to the fact that the vast majority of computational models of human physiology (and pathophysiology) have been designed with the adult forms of the disorder or disease under study; in the next cycle, we will devote significant effort to developing models that pertain more specifically to the pediatric manifestations of these multi-factor disorders. A third focus is translate the computational methods and models that we have developed in this core project into clinical applications (biophysical markers) that can be used for early disease detection, noninvasive assessment of disease severity, and therapeutic decision- making.